After earning her degree from Harvard, she worked as an assistant film editor on the Frederick Wiseman documentary, Basic Training. From 1972 to 1974 she worked for New York public schools, running workshops for teachers and children in the Bronx and designing photography curriculum for 4th-6th graders. She also worked for the State Arts Commissions of South Carolina and Mississippi setting up photography programs in rural schools. She also worked as a consultant for Polaroid and the Center for Understanding Media in New York City.[3]

Her first major photography project documented strippers at New England fairs and carnivals, which she worked on during summers while teaching in New York public schools. The project resulted in an exhibition at the Whitney Museum and a book, Carnival Strippers, which incorporated audio interviews with the subjects on a CD packaged with the book.

In the late 1970s Meiselas also documented the insurrection in Nicaragua and human rights issues in Latin America. Her most famous photograph from this project was Molotov Man, depicting a man (later found to be called Pablo 'Bareta' Aruaz) poised to throw a molotov cocktail, made from a Pepsi bottle, in his right hand, while holding a rifle in his left.[4] This became famous in its Nicaraguan context as a symbol of the Sandanista revolution, and was widely reproduced and remixed in Nicaragua. Latterly, outside this context, it was reproduced via an internet meme based on Joy Garnett's 2003 reproduction Molotov, becoming a prominent case-study of re-use of art.[5] In 2007, Harper Magazine published an article titled, On the Rights of Molotov Man.[6] This article is a collaboration between Susan Meiselas and Joy Garnett on the topic of the use of Meiselas's photo in Garnett's gallery showing.

In 1981, she visited a village destroyed by the armed forces in El Salvador and took pictures of the El Mozote massacre, working with journalists Raymond Bonner and Alma Guillermoprieto. Her photographs of the Nicaraguan Revolution have been incorporated into local textbooks in Nicaragua. Her 1991 documentary "Pictures from a Revolution" depicts her return to sites she photographed and conversations with subjects of the photographs as they reflect on the images 10 years after the war.[7] In 2004, Meiselas returned to Nicaragua and installed 19 mural sized images of her photographs on the original locations where they were taken. The project was called "Reframing History."[8]

Beginning in 1992, she used MacArthur Foundation funding to curate a photographic history of Kurdistan, resulting in the book Kurdistan: In the Shadow of History and a corresponding website.

"I don’t want to relinquish the role and the necessity of witnessing and the photographic act as a response, a responsible response. But I also don’t want to assume in a kind of naïve way … that the act of the making of the image is enough. What’s enough? And what can we know in this process of making, publishing, reproducing, exposing, and recontextualizing work in book or exhibition form? … I can only hope that it registers a number of questions."[9]